{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,6]],"date-time":"2026-07-06T11:16:28Z","timestamp":1783336588879,"version":"3.54.6"},"reference-count":40,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2026,1,7]],"date-time":"2026-01-07T00:00:00Z","timestamp":1767744000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"INAIL Research","award":["BRIC 2022 ID 52"],"award-info":[{"award-number":["BRIC 2022 ID 52"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Toxics"],"abstract":"<jats:p>In this study, for the first time urinary NMR-based metabolomics was applied to investigate the physiological alterations associated with occupational exposure in ceramic manufacturing workers. Multivariate analysis revealed a distinctive metabolic signature with exposure, characterized by a depletion of both aliphatic and aromatic amino acids and a concomitant accumulation of branched-chain amino acid catabolites. Alterations in tricarboxylic acid (TCA) cycle intermediates, including citrate and succinate, suggest an involvement of mitochondrial energy metabolism, reflecting adaptive responses to oxidative stress and increased protein turnover. Notably, glycine levels were found increased, consistent with its central role in antioxidant defense and xenobiotic detoxification. Furthermore, changes in urinary host\u2013microbiome co-metabolites, such as 4-hydroxyphenylacetate and phenylacetylglycine, indicate the potential modulation of gut microbial activity in response to occupational exposure. While limited by the small cohort, this study demonstrates the feasibility of NMR-based urinary metabolomics for the non-invasive biomonitoring of workers and suggests its potential as a useful tool for detecting subtle metabolic perturbations associated with complex occupational exposures.<\/jats:p>","DOI":"10.3390\/toxics14010056","type":"journal-article","created":{"date-parts":[[2026,1,7]],"date-time":"2026-01-07T12:34:21Z","timestamp":1767789261000},"page":"56","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Unveiling the Metabolic Fingerprint of Occupational Exposure in Ceramic Manufactory Workers"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1242-3954","authenticated-orcid":false,"given":"Michele","family":"De Rosa","sequence":"first","affiliation":[{"name":"Department of Chemistry, Sapienza University of Rome, Piazzale Aldo Moro 5, 00185 Rome, Italy"},{"name":"NMR-Based Metabolomics Laboratory, Sapienza University of Rome, Piazzale Aldo Moro 5, 00185 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4360-0140","authenticated-orcid":false,"given":"Silvia","family":"Canepari","sequence":"additional","affiliation":[{"name":"Department of Environmental Biology, Sapienza University of Rome, Piazzale Aldo Moro 5, 00185 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8973-6046","authenticated-orcid":false,"given":"Giovanna","family":"Tranfo","sequence":"additional","affiliation":[{"name":"Department of Medicine, Epidemiology, Environmental and Occupational Hygiene, National Institute for Insurance against Accidents at Work (INAIL), Via Fontana Candida 1, 00078 Monte Porzio Catone, 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Health, Medicine and Life Sciences, Department of Pharmacology and Toxicology, Maastricht University, 6200 MD Maastricht, The Netherlands"},{"name":"School of Nutrition & Translational Research in Metabolism (NUTRIM), Maastricht University, 6211 LK Maastricht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8266-1117","authenticated-orcid":false,"given":"Federico","family":"Marini","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Sapienza University of Rome, Piazzale Aldo Moro 5, 00185 Rome, Italy"},{"name":"NMR-Based Metabolomics Laboratory, Sapienza University of Rome, Piazzale Aldo Moro 5, 00185 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9599-5722","authenticated-orcid":false,"given":"Lorenzo","family":"Massimi","sequence":"additional","affiliation":[{"name":"Department of Environmental Biology, Sapienza University of Rome, Piazzale 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(2023). The Italian Ceramic Industry Recorded Revenues of \u20ac8.7 Billion in 2022, FX Design."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"602","DOI":"10.1111\/jdv.17909","article-title":"Characterizing the Relationships between Patient-reported Outcomes and Clinician Assessments of Alopecia Areata in a Phase 2a Randomized Trial of Ritlecitinib and Brepocitinib","volume":"36","author":"Winnette","year":"2022","journal-title":"J. Eur. Acad. Dermatol. Venereol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1179\/2049396714Y.0000000078","article-title":"Evaluation of Workplace Exposure to Respirable Crystalline Silica in Italy","volume":"20","author":"Scarselli","year":"2014","journal-title":"Int. J. Occup. Environ. Health"},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Nemery, B. (2006). OCCUPATIONAL DISEASES|Overview. Encyclopedia of Respiratory Medicine, Academic Press.","DOI":"10.1016\/B0-12-370879-6\/00269-6"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"706","DOI":"10.1080\/15428119891010884","article-title":"Kiln Emissions and Potters\u2019 Exposures","volume":"59","author":"Hirtle","year":"1998","journal-title":"Am. Ind. Hyg. Assoc. J."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"306","DOI":"10.5271\/sjweh.2603","article-title":"The Ceramics Industry and Lead Poisoning. Lead Poisoning in Relation to Technology and Jobs","volume":"6","author":"Brighenti","year":"1980","journal-title":"Scand. J. Work. Environ. Health"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1054","DOI":"10.1038\/4551054a","article-title":"Systems Biology: Metabonomics","volume":"455","author":"Nicholson","year":"2008","journal-title":"Nature"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Emwas, A.-H., Roy, R., McKay, R.T., Tenori, L., Saccenti, E., Gowda, G.A.N., Raftery, D., Alahmari, F., Jaremko, L., and Jaremko, M. (2019). NMR Spectroscopy for Metabolomics Research. Metabolites, 9.","DOI":"10.3390\/metabo9070123"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"2692","DOI":"10.1038\/nprot.2007.376","article-title":"Metabolic Profiling, Metabolomic and Metabonomic Procedures for NMR Spectroscopy of Urine, Plasma, Serum and Tissue Extracts","volume":"2","author":"Beckonert","year":"2007","journal-title":"Nat. Protoc."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"De Rosa, M., Giampaoli, O., Patriarca, A., Marini, F., Pietroiusti, A., Ippoliti, L., Paolino, A., Militello, A., Fetoni, A.R., and Sisto, R. (2025). Urinary Metabolomics of Plastic Manufacturing Workers: A Pilot Study. J. Xenobiotics, 15.","DOI":"10.3390\/jox15020039"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"190","DOI":"10.1016\/j.jmr.2009.11.012","article-title":"icoshift: A Versatile Tool for the Rapid Alignment of 1D NMR Spectra","volume":"202","author":"Savorani","year":"2010","journal-title":"J. Magn. Reson."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"3783","DOI":"10.1021\/ac7025964","article-title":"NMR-Based Characterization of Metabolic Alterations in Hypertension Using an Adaptive, Intelligent Binning Algorithm","volume":"80","author":"Sinnaeve","year":"2008","journal-title":"Anal. Chem."},{"key":"ref_13","unstructured":"(2024, December 04). BMRB\u2014Biological Magnetic Resonance Bank. Available online: https:\/\/bmrb.io\/."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"D622","DOI":"10.1093\/nar\/gkab1062","article-title":"HMDB 5.0: The Human Metabolome Database for 2022","volume":"50","author":"Wishart","year":"2022","journal-title":"Nucleic Acids Res."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1016\/S0009-8981(97)00110-1","article-title":"1H NMR Spectra of Normal Urines: Reference Ranges of the Major Metabolites","volume":"265","author":"Zuppi","year":"1997","journal-title":"Clin. Chim. Acta"},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Piras, C., Pibiri, M., Leoni, V.P., Cabras, F., Restivo, A., Griffin, J.L., Fanos, V., Mussap, M., Zorcolo, L., and Atzori, L. (2020). Urinary 1H-NMR Metabolic Signature in Subjects Undergoing Colonoscopy for Colon Cancer Diagnosis. Appl. Sci., 10.","DOI":"10.3390\/app10165401"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Bouatra, S., Aziat, F., Mandal, R., Guo, A.C., Wilson, M., Knox, C., Bjorndahl, T., Krishnamurthy, R., Saleem, F., and Liu, P. (2013). The Human Urine Metabolome. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0073076"},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Pulido, N., Guevara-Morales, J.M., Rodriguez-L\u00f3pez, A., Pulido, \u00c1., D\u00edaz, J., Edrada-Ebel, R.A., and Echeverri-Pe\u00f1a, O.Y. (2021). 1H-Nuclear Magnetic Resonance Analysis of Urine as Diagnostic Tool for Organic Acidemias and Aminoacidopathies. Metabolites, 11.","DOI":"10.3390\/metabo11120891"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"232","DOI":"10.1002\/cem.2790","article-title":"Unsupervised Random Forest: A Tutorial with Case Studies","volume":"30","author":"Afanador","year":"2016","journal-title":"J. Chemom."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1198\/106186006X94072","article-title":"Unsupervised Learning with Random Forest Predictors","volume":"15","author":"Shi","year":"2006","journal-title":"J. Comput. Graph. Stat."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1007\/s11306-011-0330-3","article-title":"Double-Check: Validation of Diagnostic Statistics for PLS-DA Models in Metabolomics Studies","volume":"8","author":"Saccenti","year":"2012","journal-title":"Metabolomics"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1007\/s00204-024-03903-2","article-title":"Heavy Metals: Toxicity and Human Health Effects","volume":"99","author":"Jomova","year":"2025","journal-title":"Arch. Toxicol."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Koyama, H., Kamogashira, T., and Yamasoba, T. (2024). Heavy Metal Exposure: Molecular Pathways, Clinical Implications, and Protective Strategies. Antioxidants, 13.","DOI":"10.3390\/antiox13010076"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"6894","DOI":"10.3390\/ijms12106894","article-title":"Metal-Induced Oxidative Stress and Plant Mitochondria","volume":"12","author":"Keunen","year":"2011","journal-title":"Int. J. Mol. Sci."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"136063","DOI":"10.1100\/2012\/136063","article-title":"Mitochondrial Electron Transport Chain in Heavy Metal-Induced Neurotoxicity: Effects of Cadmium, Mercury, and Copper","volume":"2012","author":"Belyaeva","year":"2012","journal-title":"Sci. World J."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1186\/s12989-020-00370-2","article-title":"Crystalline Silica Particles Cause Rapid NLRP3-Dependent Mitochondrial Depolarization and DNA Damage in Airway Epithelial Cells","volume":"17","author":"Wu","year":"2020","journal-title":"Part. Fibre Toxicol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1002\/jat.4517","article-title":"The Role of Mitochondrial Dysfunction in Macrophages on SiO2-Induced Pulmonary Fibrosis: A Review","volume":"44","author":"Zhao","year":"2024","journal-title":"J. Appl. Toxicol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"129969","DOI":"10.1016\/j.chemosphere.2021.129969","article-title":"Oxidative Stress- and Mitochondrial Dysfunction-Mediated Cytotoxicity by Silica Nanoparticle in Lung Epithelial Cells from Metabolomic Perspective","volume":"275","author":"Zhao","year":"2021","journal-title":"Chemosphere"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"926","DOI":"10.1016\/j.envpol.2017.10.060","article-title":"Mitochondrial Dysfunction, Perturbations of Mitochondrial Dynamics and Biogenesis Involved in Endothelial Injury Induced by Silica Nanoparticles","volume":"236","author":"Guo","year":"2018","journal-title":"Environ. Pollut."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1378","DOI":"10.3889\/oamjms.2022.9381","article-title":"Exposure Time of Silica Dust and the Incidence of Oxidative Stress, Inflammation, and Fibrosis in Rat Lungs","volume":"10","author":"Artana","year":"2022","journal-title":"Open Access Maced. J. Med. Sci."},{"key":"ref_31","first-page":"153","article-title":"Oxidative Stress Biomarkers in Exhaled Breath of Workers Exposed to Crystalline Silica Dust by SPME-GC-MS","volume":"16","author":"Jalali","year":"2016","journal-title":"J. Res. Health Sci."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"688","DOI":"10.1080\/15287394.2017.1286923","article-title":"Effects of Occupational Silica Exposure on OXIDATIVE Stress and Immune System Parameters in Ceramic Workers in TURKEY","volume":"80","author":"Anlar","year":"2017","journal-title":"J. Toxicol. Environ. Health Part A"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"162726","DOI":"10.1016\/j.scitotenv.2023.162726","article-title":"Oxidative Stress Indices Induced by Industrial and Urban PM2.5-Bound Metals in A549 Cells","volume":"877","author":"Barzgar","year":"2023","journal-title":"Sci. Total Environ."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Li, Q., and Hoppe, T. (2023). Role of Amino Acid Metabolism in Mitochondrial Homeostasis. Front. Cell Dev. Biol., 11.","DOI":"10.3389\/fcell.2023.1127618"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"102838","DOI":"10.1016\/j.jbc.2022.102838","article-title":"Regulation and Function of the Mammalian Tricarboxylic Acid Cycle","volume":"299","author":"Arnold","year":"2023","journal-title":"J. Biol. Chem."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"e2202934119","DOI":"10.1073\/pnas.2202934119","article-title":"A Gut Microbial Metabolite of Dietary Polyphenols Reverses Obesity-Driven Hepatic Steatosis","volume":"119","author":"Osborn","year":"2022","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1016\/j.chom.2022.11.015","article-title":"Two Distinct Gut Microbial Pathways Contribute to Meta-Organismal Production of Phenylacetylglutamine with Links to Cardiovascular Disease","volume":"31","author":"Zhu","year":"2023","journal-title":"Cell Host Microbe"},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Lee, Y.-T., Huang, S.-Q., Lin, C.-H., Pao, L.-H., and Chiu, C.-H. (2022). Quantification of Gut Microbiota Dysbiosis-Related Organic Acids in Human Urine Using LC-MS\/MS. Molecules, 27.","DOI":"10.3390\/molecules27175363"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"512","DOI":"10.1038\/s41467-023-36138-3","article-title":"Host-Microbe Co-Metabolism via MCAD Generates Circulating Metabolites Including Hippuric Acid","volume":"14","author":"Pruss","year":"2023","journal-title":"Nat. Commun."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"862","DOI":"10.1016\/j.cell.2020.02.016","article-title":"A Cardiovascular Disease-Linked Gut Microbial Metabolite Acts via Adrenergic Receptors","volume":"180","author":"Nemet","year":"2020","journal-title":"Cell"}],"container-title":["Toxics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2305-6304\/14\/1\/56\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,7]],"date-time":"2026-01-07T12:47:29Z","timestamp":1767790049000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2305-6304\/14\/1\/56"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1,7]]},"references-count":40,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,1]]}},"alternative-id":["toxics14010056"],"URL":"https:\/\/doi.org\/10.3390\/toxics14010056","relation":{},"ISSN":["2305-6304"],"issn-type":[{"value":"2305-6304","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1,7]]}}}